PROJECT SUMMARY/ABSTRACT The PhenX Toolkit is a catalog of standard measures and associated bioinformatics tools intended to help investigators improve the quality and consistency of data collection and to identify opportunities for collaborative research. Evolving over time, the PhenX Toolkit has expanded beyond the initial focus on genome-wide association studies of common, complex diseases to include rare genetic conditions, Substance Abuse and Addiction, Mental Health, Sickle Cell Disease, and Tobacco Regulatory Research. The PhenX Toolkit currently includes 476 measures, which encompass 629 protocols, and more than 22,500 variables. Over the next 5 years, we propose several significant and innovative updates to the PhenX Toolkit to further support users and to meet the evolving needs of the research community. These include expanding the existing Toolkit ontology and implementing a graph (i.e., semantic or ontological) database to support improved navigation and the development of new bioinformatics tools to visualize the content of measures and identify opportunities for cross-study collaboration. The PhenX multidisciplinary team of researchers and developers, together with input from the scientific community, will increase the utility and impact of the PhenX Toolkit through the following Specific Aims. Overall Specific Aim 4: Link PhenX measures to established ontologies: The extended PhenX ontology (based on existing ontologies) will be implemented on the cloud and will enable nimble navigation and the development of tools for users to link and harmonize variables across studies. Overall Specific Aim 5: Provide new tools that investigators need: Develop an enriched interface that can traverse the increasing complexity of the Toolkit, support access by mobile devices, and leverage the PhenX ontology to develop novel tools for comparing measures and variables. Develop Faceted Navigation: The expanded PhenX ontology and implementation of a graph database will enable development of Toolkit faceted navigation to provide an interactive exploration of the PhenX measures. Develop Concept Visualization Tool: We will leverage the PhenX ontology to develop a Concept Visualization Tool for comparing the content of PhenX measures. The Concept Visualization Tool will enable users to determine which measure is most appropriate for their study and will help the PhenX Steering Committee and Working Groups identify gaps and redundancies. Develop Connect the Studies Tool: We will leverage the mappings between PhenX variables and the database of Genotypes and Phenotypes (dbGaP) and the extended PhenX ontology to develop the Connect the Studies Tool. For each PhenX variable, the Connect the Studies Tool will present users with the number of study participants associated with a specific level of data similarity. These technology updates and novel bioinformatics tools will reduce barriers to translational research, increase the consistency and quality of data collection, and revolutionize the way investigators think about data harmonization.